Inflammatory defects caused by GPI-anchor deficiency in macrophages

Abstract

The function of the glycosyl phosphatidylinositol (GPI)-anchor on macrophages was studied using myeloid-specific GPI-anchor knock-out mice, which were generated by conditional targeting of PigA in the myeloid lineage. Alveolar macrophages from these mice displayed a GPI-anchor negative phenotype, as determined by the lack of heat stable antigen and CD48 on their surface. These macrophages did not produce the proinflammatory cytokine tumor necrosis factor (TNF)-α in response to a low concentration of lipopolysaccharide in vitro. After induction of immune complex-mediated alveolitis, an in vivo model for inflammation, several inflammatory processes were impaired in these mice, including local production of the macrophage-derived proinflammatory cytokines TNF-α and interleukin-6, subsequent neutrophil infiltration, and hemorrhage. Together, these observations indicate that the GPI-anchor on macrophages serves a nonredundant stimulatory function in inflammation, triggered either through the innate or the acquired immune system.